Davis Lab: Research

The evolution of limbs from paired fins during the vertebrate invasion of land has inspired the imagination and scientific curiosity of biologists for nearly two centuries.  In current models, paired fins are patterned by distinct proximal and distal developmental modules, generating adult skeletal compartments containing either endochondral or dermal elements respectively.  Emphasis on formation of skeletal type led to the hypothesis that fin-folds in fish and autopods (hands/feet) in terrestrial vertebrates are not homologous, patterned by different developmental modules, despite similar distal positions in the appendage.  Recent developmental studies in our lab using two phylogenetically well-positioned vertebrates, the American paddlefish (Polyodon spathula) and the small spotted catshark (Scyliorhinus canicula) have uncovered evidence of an ancient and conserved gene regulatory network shared by fin-folds and autopods, raising the intriguing alternative hypothesis that these structures share a deep regulatory homology.  

 

HoxD expression in paddlefish & catshark fin-folds:  implications for paired appendage evolution 

The role of Homeobox transcription factors during fin and limb development have been the focus of recent work investigating the evolutionary origin of limb-specific morphologies. We characterized the expression of HoxD genes, as well as the cluster-associated genes Evx2 and LNP, in paddlefish. Our results demonstrate a collinear pattern of nesting in early fin buds that includes HoxD14, a gene previously thought to be isolated from global Hox regulation. We also show that in both paddlefish and catshark late phase HoxD transcripts are present in cells of the fin-fold and co-localize with And1, a component of the dermal skeleton. These new data support an ancestral role for HoxD genes in patterning the fin-folds of jawed vertebrates, and fuel new hypotheses about the evolution of cluster regulation and the potential downstream differentiation outcomes of distinct HoxD-regulated compartments.

 

Evolution of fin-fold compartments and the Shh/LIM/Gremlin/Fgf transcriptional network

The evolutionary origin of the autopod involved a loss of the fin-fold and associated dermal skeleton with a concomitant elaboration of the distal endoskeleton to form a wrist and digits. Developmental studies, primarily from teleosts and amniotes, suggest a model for appendage evolution in which a delay in the AER-to-fin-fold conversion fuelled endoskeletal expansion by prolonging the function of AER-mediated regulatory networks. We characterized aspects of paired fin development in paddlefish and catshark to explore aspects of this model in a broader phylogenetic context. Our data demonstrate that in basal gnathostomes, the autopod marker HoxA13 co-localizes with the dermoskeleton component And1 to mark the position of the fin-fold, supporting recent work demonstrating a role for HoxA13 in zebrafish fin ray development. Additionally, we show that in paddlefish, the proximal fin and fin-fold mesenchyme share a common mesodermal origin, and that components of the Shh/LIM/Gremlin/Fgf transcriptional network critical to limb bud outgrowth and patterning are expressed in the fin-fold with a profile similar to that of tetrapods. Together these data draw contrast with hypotheses of AER heterochrony and suggest that limb-specific morphologies arose through evolutionary changes in the differentiation outcome of conserved early distal patterning compartments.